(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster discussion session focused on Kidney and Bladder cancers on Saturday evening included a presentation from Dr. Nieves Martinez Chanza discussing the role of avelumab as a neoadjuvant treatment in patients with non-metastatic muscle invasive bladder cancer (MIBC).
Cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy is the standard of care for patients with localized MIBC. However, many patients are ineligible for cisplatin and there are no proven agents with benefits in the neoadjuvant setting. Thus, these patients are recommended to proceed directly to cystectomy. However, novel treatment paradigms may offer the potential for these patients to benefit from neoadjuvant treatment. Immunotherapy has an increasingly large role in the treatment of urothelial carcinoma and is therefore being explored in the neoadjuvant setting.
The AURA (Oncodistinct-004) trial assesses the role of avelumab, a monoclonal antibody directed against PD-L1, as preoperative therapy in two distinct cohorts, patients who are eligible for cisplatin-based chemotherapy and those who are not. Results of this work in the cisplatin-eligible cohort have been previously presented at ESMO 2021 but Dr. Nieves Martinez Chanza provided results of the cisplatin-ineligible cohort here.
The AURA trial is a prospective, multicenter, randomized, phase II trial for patients with cT2-4aN0-2M0 bladder carcinoma, with accrual and treatment stratified by eligibility for cisplatin chemotherapy. Among those patients who were cisplatin ineligible, 1:1 randomization was performed between 4 cycles of paclitaxel-gemcitabine (PG) plus avelumab every 2 weeks or 4 cycles of avelumab every 2 weeks.
The primary study endpoint was pathological complete response (pCR) rate (ypT0/isN0) with the objective, in each arm, to show pCR rate > 5%. The study would have 90% statistical power if the pCR rate exceeded 25%. A two-step design was used with planned interim analysis after 12 evaluable patients in each arm. Beyond pathological complete response, secondary endpoints were pathologic downstaging rate (< ypT2N0) and safety.
The authors included 56 cisplatin-ineligible patients who were evaluable, 28 of whom were randomized to PG + avelumab and 28 of whom were randomized to avelumab alone. Which each arm was 93% men, those in the PG + avelumab arm were somewhat younger [median age 72 years (41-80) versus 75 years (49-89)]. One patient in the avelumab alone arm did not undergo surgery due to progression but was included in intention to treat analysis.
Five patients did not receive the planned 4 cycles of treatment: three patients in the PG + avelumab arm experienced toxicity which precluded completing the schedule therapy and 2 patients in the avelumab arm ceased treatment early due to patient/physician decision. A pathological complete response (pCR) was achieved in 5 patients (18%; 95%CI 6%-37%) treated with PG + avelumab and 10 patients (36%; 95%CI 19%-56%) treated with avelumab. Downstaging to < ypT2N0 was achieved in 6 patients (21%; 95%CI 8%-41%) treated with PG + avelumab and 11 patients (39%; 95%CI 22%-59%) treated with avelumab alone.
The median time from treatment initiation to surgery was 82 days (55-144) for those receiving PG + avelumab and 67 days (38-89) for those receiving avelumab alone.
The most common irAEs of any grade were asthenia (15%), skin toxicity and myalgia/arthralgia (each 5%). Two patients in the PG + avelumab arm experienced grade 3 irAEs (hepatitis and pneumonitis), which resulted in avelumab discontinuation for 1 patient. No treatment-related deaths were reported.
The authors conclude that, in this group of cisplatin-ineligible patients, neoadjuvant avelumab monotherapy resulted in high pCR and was safely administered without compromising surgical resection. Further follow-up of this cohort is ongoing.
Presented by: Nieves Martinez Chanza, MD, PhD, medical oncologist Oncology Medicine Department at Jules Bordet Cancer Institute, Brussels, Belgium